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An Investigational Drug, PF-02341066 Is Being Studied Versus Standard Of Care In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00932893
First received: June 30, 2009
Last updated: October 31, 2016
Last verified: October 2016
Results First Received: March 13, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Carcinoma, Non-Small-Cell Lung
Interventions: Drug: PF-02341066
Drug: Pemetrexed
Drug: Docetaxel

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Crizotinib Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Chemotherapy Pemetrexed 500 mg per square meter (mg/m^2) intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.

Participant Flow:   Overall Study
    Crizotinib   Chemotherapy
STARTED   173   174 
Treated   172   171 
COMPLETED   40   4 
NOT COMPLETED   133   170 
Death                115                24 
Lost to Follow-up                8                0 
Withdrawal by Subject                5                2 
Unspecified                5                144 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS) included all participants who were randomized to study treatment.

Reporting Groups
  Description
Crizotinib Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Chemotherapy Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Total Total of all reporting groups

Baseline Measures
   Crizotinib   Chemotherapy   Total 
Overall Participants Analyzed 
[Units: Participants]
 173   174   347 
Age 
[Units: Years]
Mean (Standard Deviation)
 50.3  (13.1)   49.8  (13.0)   50.0  (13.0) 
Gender 
[Units: Participants]
Count of Participants
     
Female      98  56.6%      95  54.6%      193  55.6% 
Male      75  43.4%      79  45.4%      154  44.4% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Progression-Free Survival (PFS)   [ Time Frame: Randomization until progressive disease (PD) or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: Randomization until death (up to 4.5 years) ]

3.  Secondary:   Overall Survival Probability at Months 6 and 12   [ Time Frame: Month 6, 12 ]

4.  Secondary:   Percentage of Participants With Objective Response (OR)   [ Time Frame: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

5.  Secondary:   Percentage of Participants With Disease Control at Week 6   [ Time Frame: Week 6 ]

6.  Secondary:   Percentage of Participants With Disease Control at Week 12   [ Time Frame: Week 12 ]

7.  Secondary:   Duration of Response (DR)   [ Time Frame: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

8.  Secondary:   Time to Tumor Response (TTR)   [ Time Frame: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

9.  Secondary:   Plasma Concentration of Crizotinib   [ Time Frame: Pre-dose on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of Cycles 2, 3, 5 ]

10.  Secondary:   Number of Participants With Categorical Maximum QTcF for Crizotinib   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 1, 2 ]

11.  Secondary:   Plasma Concentration of Soluble c-Met Ectodomain and Hepatocyte Growth Factor Scatter Proteins   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 2, end of treatment (up to 112 weeks) ]

12.  Secondary:   Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough   [ Time Frame: Baseline up to end of treatment (up to 112 weeks) ]

13.  Secondary:   European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)   [ Time Frame: Baseline, Day (D) 1 of each cycle (C) until disease progression, end of treatment (EOT, up to 112 weeks) ]

14.  Secondary:   European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13)   [ Time Frame: Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks) ]

15.  Secondary:   European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)   [ Time Frame: Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks) ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame Active reporting period is from the time of informed consent until at least 28 days after the last dose of study treatment.
Additional Description All causality (serious and non-serious) adverse events have been reported. Non-serious adverse events above the 5% threshold are reported herein.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Crizotinib Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Chemotherapy Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.

Other Adverse Events
    Crizotinib   Chemotherapy
Total, Other (not including serious) Adverse Events     
# participants affected / at risk   172/172 (100.00%)   169/171 (98.83%) 
Blood and lymphatic system disorders     
Anaemia * 1     
# participants affected / at risk   36/172 (20.93%)   27/171 (15.79%) 
Leukopenia * 1     
# participants affected / at risk   24/172 (13.95%)   9/171 (5.26%) 
Neutropenia * 1     
# participants affected / at risk   41/172 (23.84%)   18/171 (10.53%) 
Cardiac disorders     
Bradycardia * 1     
# participants affected / at risk   9/172 (5.23%)   0/171 (0.00%) 
Eye disorders     
Photopsia * 1     
# participants affected / at risk   21/172 (12.21%)   1/171 (0.58%) 
Vision blurred * 1     
# participants affected / at risk   13/172 (7.56%)   5/171 (2.92%) 
Visual impairment * 1     
# participants affected / at risk   74/172 (43.02%)   8/171 (4.68%) 
Lacrimation increased * 1     
# participants affected / at risk   1/172 (0.58%)   9/171 (5.26%) 
Gastrointestinal disorders     
Abdominal pain * 1     
# participants affected / at risk   18/172 (10.47%)   8/171 (4.68%) 
Abdominal pain upper * 1     
# participants affected / at risk   17/172 (9.88%)   13/171 (7.60%) 
Constipation * 1     
# participants affected / at risk   83/172 (48.26%)   39/171 (22.81%) 
Diarrhoea * 1     
# participants affected / at risk   106/172 (61.63%)   34/171 (19.88%) 
Dyspepsia * 1     
# participants affected / at risk   18/172 (10.47%)   6/171 (3.51%) 
Nausea * 1     
# participants affected / at risk   104/172 (60.47%)   60/171 (35.09%) 
Stomatitis * 1     
# participants affected / at risk   9/172 (5.23%)   13/171 (7.60%) 
Vomiting * 1     
# participants affected / at risk   88/172 (51.16%)   32/171 (18.71%) 
Dysphagia * 1     
# participants affected / at risk   9/172 (5.23%)   2/171 (1.17%) 
Gastrooesophageal reflux disease * 1     
# participants affected / at risk   12/172 (6.98%)   0/171 (0.00%) 
General disorders     
Asthenia * 1     
# participants affected / at risk   31/172 (18.02%)   32/171 (18.71%) 
Chest pain * 1     
# participants affected / at risk   15/172 (8.72%)   13/171 (7.60%) 
Fatigue * 1     
# participants affected / at risk   51/172 (29.65%)   60/171 (35.09%) 
Oedema * 1     
# participants affected / at risk   15/172 (8.72%)   6/171 (3.51%) 
Oedema peripheral * 1     
# participants affected / at risk   59/172 (34.30%)   15/171 (8.77%) 
Pyrexia * 1     
# participants affected / at risk   41/172 (23.84%)   33/171 (19.30%) 
Pain * 1     
# participants affected / at risk   10/172 (5.81%)   9/171 (5.26%) 
Infections and infestations     
Nasopharyngitis * 1     
# participants affected / at risk   32/172 (18.60%)   7/171 (4.09%) 
Upper respiratory tract infection * 1     
# participants affected / at risk   24/172 (13.95%)   14/171 (8.19%) 
Injury, poisoning and procedural complications     
Fall * 1     
# participants affected / at risk   11/172 (6.40%)   3/171 (1.75%) 
Investigations     
Alanine aminotransferase increased * 1     
# participants affected / at risk   72/172 (41.86%)   21/171 (12.28%) 
Aspartate aminotransferase increased * 1     
# participants affected / at risk   55/172 (31.98%)   17/171 (9.94%) 
Blood alkaline phosphatase increased * 1     
# participants affected / at risk   18/172 (10.47%)   6/171 (3.51%) 
Blood creatinine increased * 1     
# participants affected / at risk   13/172 (7.56%)   3/171 (1.75%) 
Neutrophil count decreased * 1     
# participants affected / at risk   15/172 (8.72%)   9/171 (5.26%) 
Weight decreased * 1     
# participants affected / at risk   21/172 (12.21%)   8/171 (4.68%) 
White blood cell count decreased * 1     
# participants affected / at risk   16/172 (9.30%)   13/171 (7.60%) 
Electrocardiogram QT prolonged * 1     
# participants affected / at risk   9/172 (5.23%)   0/171 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1     
# participants affected / at risk   56/172 (32.56%)   46/171 (26.90%) 
Hyperglycaemia * 1     
# participants affected / at risk   12/172 (6.98%)   9/171 (5.26%) 
Hypoalbuminaemia * 1     
# participants affected / at risk   16/172 (9.30%)   1/171 (0.58%) 
Hypokalaemia * 1     
# participants affected / at risk   15/172 (8.72%)   5/171 (2.92%) 
Hypocalcaemia * 1     
# participants affected / at risk   13/172 (7.56%)   0/171 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1     
# participants affected / at risk   15/172 (8.72%)   20/171 (11.70%) 
Back pain * 1     
# participants affected / at risk   30/172 (17.44%)   11/171 (6.43%) 
Musculoskeletal pain * 1     
# participants affected / at risk   14/172 (8.14%)   6/171 (3.51%) 
Myalgia * 1     
# participants affected / at risk   5/172 (2.91%)   19/171 (11.11%) 
Pain in extremity * 1     
# participants affected / at risk   20/172 (11.63%)   10/171 (5.85%) 
Muscle spasms * 1     
# participants affected / at risk   9/172 (5.23%)   4/171 (2.34%) 
Neck pain * 1     
# participants affected / at risk   11/172 (6.40%)   5/171 (2.92%) 
Nervous system disorders     
Dizziness * 1     
# participants affected / at risk   34/172 (19.77%)   13/171 (7.60%) 
Dysgeusia * 1     
# participants affected / at risk   45/172 (26.16%)   17/171 (9.94%) 
Headache * 1     
# participants affected / at risk   46/172 (26.74%)   26/171 (15.20%) 
Neuropathy peripheral * 1     
# participants affected / at risk   5/172 (2.91%)   10/171 (5.85%) 
Paraesthesia * 1     
# participants affected / at risk   13/172 (7.56%)   7/171 (4.09%) 
Peripheral sensory neuropathy * 1     
# participants affected / at risk   9/172 (5.23%)   6/171 (3.51%) 
Visual perseveration * 1     
# participants affected / at risk   12/172 (6.98%)   0/171 (0.00%) 
Psychiatric disorders     
Insomnia * 1     
# participants affected / at risk   19/172 (11.05%)   13/171 (7.60%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1     
# participants affected / at risk   37/172 (21.51%)   35/171 (20.47%) 
Dyspnoea * 1     
# participants affected / at risk   27/172 (15.70%)   29/171 (16.96%) 
Epistaxis * 1     
# participants affected / at risk   3/172 (1.74%)   10/171 (5.85%) 
Haemoptysis * 1     
# participants affected / at risk   9/172 (5.23%)   11/171 (6.43%) 
Oropharyngeal pain * 1     
# participants affected / at risk   20/172 (11.63%)   7/171 (4.09%) 
Rhinorrhoea * 1     
# participants affected / at risk   4/172 (2.33%)   9/171 (5.26%) 
Productive cough * 1     
# participants affected / at risk   12/172 (6.98%)   8/171 (4.68%) 
Pulmonary embolism * 1     
# participants affected / at risk   9/172 (5.23%)   2/171 (1.17%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1     
# participants affected / at risk   21/172 (12.21%)   35/171 (20.47%) 
Dry skin * 1     
# participants affected / at risk   10/172 (5.81%)   2/171 (1.17%) 
Pruritus * 1     
# participants affected / at risk   12/172 (6.98%)   7/171 (4.09%) 
Rash * 1     
# participants affected / at risk   23/172 (13.37%)   30/171 (17.54%) 
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 18.1



  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No analyses of ALK fusion variants or protein expression were done due to limited slide stability of unstained tissue sections required for immunohistochemistry and no nucleic acid based assay was available to identify specific ALK gene fusion.


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